As for the inhibition of melanin formation, certain whitening agents such as ascorbic acid or derivatives thereof, placenta extracts, kojic acids, glutathion, hydroquinone and a derivative thereof (arbutin), and plant extracts have so far been incorporated in dermatologic preparations for skin whitening for the purpose of preventing such phenomena as sunburn-induced skin darkening or inflammation and pigmentation-due formation of spots and freckles (Fragrance Journal, Vol. 18, No. 6, 1990, pp. 47-58).
Meanwhile, elastase is a protease specifically acting on elastin, which is concerned with the tension and elasticity of the skin. This participates in decreasing the quantity of elastin, leading to particularly grave results among the skin aging phenomena. Further, ultraviolet rays activate elastase, with the results that the skin loses it tension and elasticity. The effect of elastase increases with the advance of age, bringing about the same results. Therefore, if the excessive effect of elastase can be lessened, it will become possible to prevent the skin aging due to ultraviolet rays and/or aging. From such viewpoint, substances having elastase inhibiting activity have been searched for. As a result, it has been demonstrated that extracts from Schima species, eucalyptus, and Meniran (Phylianthus niun) or Kemiri (Aleurifis moluccana), among others are effective for such purposes (JP-A-9-095420, JP-A-9-087137, and JP-A-9-087136).
As for hyaluronidase, its functions in connective tissues are considered to retain water intercellular spaces, form a jelly-like matrix in the tissue to maintain cells, maintain skin lubricity and flexibility, and protect the skin against external forces (mechanical lesions) and bacterial infection. It is said that hyaluronic acid in the skin decreases with aging, with the result that such aging phenomena as fine wrinkles formation and skin roughening. Therefore, it is considered that inhibition of the activity of hyaluronidase, which decomposes such hyaluronic acid, may contribute to the stabilization of skin hyaluronic acid and will be also effective in improving the barrier function of the skin by preventing the same from decreasing. Presumably, this also contribute to stabilization of hyaluronic acid used in preparations for the treatment of arthritis, among others, and further to stabilization of hyaluronic acid in preparations applied to the skin for improving the skin function.
Hyaluronidase is also known as an inflammatory enzyme, and it is known that inhibition of its activity is effective in reducing inflammation and that it suppresses allergy as well. Several substances capable of inhibiting hyaluronidase have been reported. Hyaluronidase inhibiting activity has been confirmed in extracts of peony root, coptis rhizome (JP-A-1-128933), ziyu (Sanguisorba officinalis), geranium herb (JP-A-2-011520), Mimusops elengi, Eugenia jambolana, Saraca indica, Mucuna birdwoodiana or Millettina nitida or dilisiana, senkakuso (agrimoniae herba), and Machilus thubergii or japonica (JP-A080553), among other herb medicines.
Active oxygen eliminators having SOD activity are widely used in the treatment and/or alleviation, for instance, of various diseases caused by active oxygen (O2−), for example circulatory disturbance-due diseases (myocardial infarct, cerebral apoplexy, hypertension, menstrual pain, muscle stiffness of shoulder, neuralgia, lumbago, hangover, etc.), adult diseases/internal diseases (cancer, nephritis, hepatitis, diabetes, etc.), cosmetic and skin diseases (spots, freckles, dry/rough skin, cold feeling, constipation, wrinkles, atopic dermatitis, etc.). They can also be used in the fields of foods, food additives, cosmetics, drugs, etc.
More specifically, there are known cosmetics in which various characteristics of SOD are utilized (e.g. JP-B59-010324, JP-A-55-087712) and dermatologic preparation compositions comprising a placenta or liver extract having stable SOD activity (JP-A61-277626). Further known as plant extracts having SOD activity are plant flavonoid-containing extracts of Cassia nomame, Lycium chinense or barbarum, Antemisia capillanes or scoparia, Alnus sieboldiana or firma, Sophora japonica, Polygonum multiforum, Cassia obtusifolia or tora, sinom nium stem, Rubia argyi, Acorus gramineus, Rosa laevigata, Taxus cuspidata (JP-A-8-283172), hibiscus, aloe, rhubarb, osei (polygonati rhizoma), bearberry leaf, enmeiso (plectranthi herba), gardenia fruit, yobaihi (nyrice cirtex), pueraria root, bupleurum root, cnidium rhizome, atractylodes lancea rhizome, mentha leaf, poria sclerotium, glycyrrhiza, peony root, sin'i (magnoalae flos), Saururus chinensis, Japanese angelica root, cinnamon bark, houttuynia herb, coptis rhizome, moutan bark, gentian, nutgall, swertia herb, geranium herb, ephedra herb, phellodendron bark, almond, dried ginger, jujube, scutellaria root, citrus unshu peel, turmeric, nindo (lonicerae folium cum caulis), apricot fruit, rehmannia root, garlic, sage, oregano, rosemary, laurel, celery, thyme, tarragon, onion, nutmeg, mace, clove, Japanese horseradish, savory, basil, red pepper, roasted bean, black tea, green tea, persimmon leaf, coffee, horsetail, henon bamboo, mugwort, low striped bamboo, matrimony vine, Cyrtomium species, shiitake mushrooms, ginkgo (JP-A-06-024937), scutellaria root, gingko, Mucuna birdwoodiana or Millettia nitida or dillsiana, sanzasi (crataegi fructus), maikaika (rosae rugosae flos), saxifrage, Melissa, geranium herb, moutan bark, parsley, tormentil, rakanka (momordicae fructus), yashajitsu (fruit of Alunus firma), and zikoppi (lycii cortex) (JP-A-10-307680).
Referring to antioxidants, sebum is secreted on the human skin to protect the same. When exposed to ultraviolet rays, for instance, this sebum is oxidized to give lipid peroxides, which irritate the skin. These lipid peroxides attack the cell membrane, damaging or adversely affecting the same in various ways, and these damages, in turn, are said to be involved in human skin aging. Therefore, it is considered effective not only in preventing the skin condition from worsening but also in preventing the living body from aging to inhibit the formation of such lipid peroxides by means of antioxidants.
Among specific antioxidants, there have been reported plants extracts such as extracts from birch (Betula platyphylla) (JP-A-10-046143) and various plant extracts obtained by extraction, with water or a lower alcohol or an aqueous lower alcohol solution, of at least one plant selected from the group consisting of hibiscus, aloe, rhubarb, osei (polygonati rhizoma), bearberry leaf, enmeiso (plectranthi herba), yobaihi (nyricae cirtex), pueraria root, cnidium rhizome, atractylodes lancea rhizome, mentha leaf, glycyrrhiza, peony root, coix seed, sin'i (magnoliae flos), cinnamon bark, houttuynia herb, coptis rhizome, moutan bark, gentian, nutgall, swertia herb, geranium herb, phellodendron bark, dried ginger, scutellaria root, chulling (poly porus), garlic, sage, oregano, rosemary, laurel, celery, thyme, tarragon, nutmeg, mace, clove, Japanese horseradish, savory, basil, red pepper, roasted bean, black tea, green tea, persimmon leaf, coffee, horsetail, henon bamboo, mugwort, Cynostemma species, low striped bamboo, matrimony vine, Cyrtomium species, and shiitake mushrooms (JP-A6-024937).
As regards the melanin formation, however, some dermatologic preparations containing these whitening agents are unsatisfactory in whitening effec, and others are effective in inhibiting melanin formation but still have problems from the safety viewpoint. In many instances, the whitening agents are denatured in the preparations, for instance, hence the desired effects are not obtained. Improvements in this respect have thus been desired.
As regards the elastase activity inhibition, if the excess elastase activity can be inhibited, it may become possible to prevent skin aging. However, the elastase inhibitors so far reported are not fully satisfactory from the viewpoint of stability, effect, and feel upon application.
As for the hyaluronidase activity inhibition, in spite of various investigations in search of cosmetic ingredients having antinflammatory or antiallergic activity, any safe and promising one has not yet been obtained. Thus, substances have been desired which are natural products and have been eaten by men for long and whose safety has thus been established and which have strong hyaluronidase inhibiting activity and further have some other effect on the skin.
The in vivo enzyme superoxide dismutase (SOD) is known as an active oxygen eliminator. However, this is difficult to purify, thermally unstable and readily deactivated, hence it is very expensive. Therefore, the advent of SOD substitutes (substances having SOD-like activity) which show active oxygen eliminating activity, like SOD and are highly stable and can be obtained at low cost has been awaited.
As for the antioxidants so far used, cosmetics and dermatologic preparations containing BHT, BHA and the like tend to cause contact dermatitis and their safety is questionable. On the other hand, gallic acid derivatives and vitamin E species are insufficient in antioxidant activity and thus fail to effectively prevent fat/oil-containing products from becoming rancid. Even if the effect of preventing skin aging due to peroxidation of skin lipids, in particular, is expected of the dermatologic preparations containing them, no satisfactory effects can be obtained.
Further, referring to the whitening effect, the direct inhibitory effect on melanin-synthesizing melanocytes as well as the effect of suppressing the production of melanocyte-stimulating agents (MSH, endotehlin, NO, histamine, PGE2, etc.) released by melanocyte-surrounding cells is an important factor. Therefore, the antinflammatory action inhibiting these stimulators from being released by keratinocytes is also considered to be effective in promoting whitening.
Furthermore, ascorbic acid derivatives and arbutin, which are whitening agents in conventional use, have themselves antioxidant activity, and it Is considered that their active oxygen- and free radical-quenching activity is party involved in the mechanisms of whitening. Therefore, herb extracts having such whitening and antioxidant activities together with antiinflammatory and other activities will be more effective. However, no investigations have so far been made in search of such herb medicine extracts having such a plurality of activities.